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Not all carcinogens are mutagens. Alcohol and estrogen, for example, does not damage DNA.

It's one of the assumptions of the Ames test that mutagenicity implies carcinogenicity, but is this always the case? I assumed that it was, but then I saw one of the comments here. I did some more research but the internet seems to be reluctant to be definitive on the subject. This guy claims 'no', but I'd prefer sources or at least a response that handles counterexamples like HPV. This paper claims 'yes', but doesn't list any specific examples. Some mutagens might be more specific to genes involved in cell cycle regulation, so I could see how a weak mutagen is a powerful carcinogen.

My question is, can you go the other way? Are there mutagens that just do not cause cancer? If they do not exist or are not known to exist, are they even possible?

WYSIWYG
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Resonating
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2 Answers2

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Short answer

All mutagens are potential carcinogens unless the mutagen is highly specific to a site. As noted in the question, carcinogens need not be mutagenic.

HPV causes oncogenic transformation of a cell because of certain proteins that it expresses. HPV is considered a carcinogen by the IARC. Some retroviruses are oncogenic: they might carry an oncogene or insert randomly near an endogenous proto-oncogene and cause oncogenic transformation; this phenomenon is called insertional mutagenesis (Coffin JM, Hughes SH, Varmus HE, editors. Retroviruses). They can also integrate within a gene and knock it out. Many of these viruses are considered carcinogens by IARC.

Hepatitis viruses (B & C) can also induce carcinogenesis but insertional mutagenesis is not the sole mechanism (Cougot et al., 2005; Fung et al., 2009; Lemon & McGivern, 2012). Hepatitis viruses are considered carcinogens by IARC.

Ethanol in alcoholic beverages is considered carcinogenic by IARC. There are many substances listed as carcinogens by IARC but they are not mutagenic. The general mechanism of carcinogenesis by these substances may be prolonged inflammation or ROS generation.

Loss of function of the tumour suppressor gene p53 leads to cancerous progression (Chiche et al., 2016; Venkatachalam et al. ISBN:978-1-59259-100-8). So an siRNA that targets p53 should be called a carcinogen. It would however not cause any mutations and is hence not a mutagen.

If you consider the tools developed for genome editing, such as ZFN, CRISPR-Cas and TALEN as mutagens then they are not carcinogenic. However the term mutagen is not used for these molecules. Mutagen almost always refers to a molecule that causes random mutagenesis thereby making it a potential carcinogen.

Community
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WYSIWYG
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I'm no expert on the matter, but just quoting from Wikipedia:

Mutagens are not necessarily carcinogens, and vice versa. Sodium Azide for example may be mutagenic (and highly toxic), but it has not been shown to be carcinogenic.

It cites Toxicology And Carcinogenesis Studies Of Sodium Azide.

So it would appear the answer is no. Not all mutagens are carcinogens.

David
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p.s.w.g
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    Sodium azide is only mutagenic part of the time(half of the strains tested), and there's http://www.ncbi.nlm.nih.gov/pubmed/2671718 this paper that shows that sodium azide isn't a mutagen in mammals. It's still poisonous (cerebral necrosis!) but neither a mutagen nor a carcinogen in mammals. – Resonating Jun 25 '14 at 16:02
  • It seems like there should be a counter-example (a mutagen with zero or negligible carcinogenicity) but I can't find one. – Resonating Jun 25 '14 at 16:04